Fetal Surgery

The Birth of a New Surgical Specialty

Not long ago, the idea of a surgeon operating on a human fetus within the womb was considered radical and heretical by the medical community. Pioneers and disciples of the burgeoning field of fetal surgery faced numerous obstacles, not the least of which was the charge that it would be unethical to violate the sanctity of the womb. Nevertheless, surgeon scientists persisted with diligent preparation, rigorous large animal modeling, and frank multidisciplinary conversation. Now, thirty years after the first human fetal intervention, fetal surgery is the standard of care for many congenital conditions.

The first open fetal surgical intervention was performed in 1981 by Dr. Michael Harrison at the University of California, San Francisco, in a fetus with obstructive uropathy. Prior to this landmark event, intrauterine procedures were limited to diagnostic interventions such as amniocentesis or limited percutaneous treatments such as intrauterine transfusion for Rh erythroblastosis. The first successful placement of a fetal vesicoamniotic shunt by Dr. Harrison and his team proved that surgeons could successfully and safely accomplish an operation in a pregnant mother and maintain the pregnancy. While the first fetal patient unfortunately died shortly after birth, the second operation was successful for both the mother and the fetus, and that second fetal patient is now a young man in his fourth decade of life.

Fetal surgery is unique in that there are two patients in every intervention. As in living-related living donor translation, one patient undergoes a life-threatening surgical procedure for no benefit to herself. The ethical considerations of the pregnant woman as an “innocent bystander” are complicated and the stakes are high. Maternal safety was, and has always been, paramount in the development of fetal surgery as a discipline. Furthermore, maternal morbidity at the time of fetal surgery and for future pregnancies is one of the most important considerations that need to be weighed against the potential benefits to the fetus. To address maternal safety, the technical aspects of fetal surgery—opening the gravid uterus without maternal hemorrhage, maintaining uterine relaxation, closing the hysterotomy in a water-tight manner, and limiting postoperative preterm labor—were all developed in rigorous animal models. Each step in the development of this discipline was a challenge and an opportunity for innovation, and it was here in the development of open fetal surgical techniques that true innovation occurred. Through multidisciplinary collaboration with neonatologists, perinatologists, radiologists, and anesthesiologists, innovation with biomedical partners, and an army of bright surgical residents, the largely nonfunded vision of open fetal surgery became a reality. Over the ensuing decades, fetal surgery techniques evolved, and the development of fetal surgery has paralleled the rise of other minimally invasive procedures in a constant attempt to balance the benefit for the fetus with the risks to the pregnant mother.

Fetal surgery is now the standard of care for several conditions, such as advanced twin-twin transfusion syndrome (TTTS) and certain cases of myelomeningocele (MMC). As the safety for women and fetuses improves and as techniques evolve, more indications will undoubtedly emerge.

Although there have been thousands of fetal procedures to date, there are few known maternal deaths worldwide that are remotely referable to a fetal procedure. This is a remarkable safety record and a credit to the slow and careful development of the field. Notably, the existence of fetal surgery is due in large part to the extraordinary bravery of the many women who were willing to endeavor something new and unknown for the improved prognosis of their future child.

Prenatal Pathophysiologic Considerations and Rationale

The original rationale for fetal surgery was based on the concept that simple anatomic defects in utero could lead to disastrous consequences in postnatal life. The hypothesis was that if one could reverse or repair the anatomy, then the physiology would also normalize once born. It turns out that this is not as straight-forward as originally postulated, as simple anatomic repairs turned out to be more complicated in practice, with fetal access and uterine closure remaining a crucial obstacle. Included in the original rationale for fetal surgery is the overarching concept that maternal safety is paramount. Originally, fetal interventions were carried out only for conditions that were uniformly lethal, as saving the fetus was thought to be of enough benefit to warrant the surgical risks to the mother. Once techniques of fetal access were standardized, open, fetoscopic, or needle-based procedures were developed based on the anatomy and subsequent physiology of each anomaly ( Box 73.1 ).

Maternal Considerations and Morbidity

Unlike most operations, fetal surgery, by definition, involves two patients undergoing surgery simultaneously. The risks and benefits between the mother and fetus must be examined closely and the benefits for the fetus must justify the risk to the mother, who gains no medical benefit from the operation. In addition, mothers must be in reasonable health in order to undergo fetal surgery. Specifically, for open fetal surgery, mothers should have no major comorbidities or contraindications for surgery. Maternal risks of fetal surgery include: bleeding, chorioamnionitis, placental abruption, preterm premature rupture of membranes (PPROM), preterm labor, and premature delivery. Furthermore, mothers undergoing open fetal surgery are subject to a hysterotomy similar to a classical Cesarean section, rather than the method of a low transverse uterine incision that is preferred for modern Cesarean sections. Due to this hysterotomy, a woman undergoing open fetal surgery is at increased risk of uterine dehiscence and uterine rupture for not only the current, but also all future pregnancies. A registry review by the North American Fetal Therapy Network (NAFTNet) demonstrated a 9.6% uterine rupture rate in a subsequent pregnancy following prior open MMC repair. While these results are similar to classical Cesarean section rates, they are no less of a concern to fetal surgeons. Due to the significant maternal risks, new techniques for minimally invasive fetoscopic repair of MMC are being developed and studied. Currently, the fetoscopic approach for MMC repair is practiced by numerous centers, with the only potential downfall of the fetoscopic approach being that it may not allow for water-tight closure of the defect as well as the open surgical approach. It remains to be seen if the fetoscopic technique can be improved to allow the same developments in the fetus as open fetal surgery. It is also the case that surgical approaches must be reoptimized with every emerging treatment innovation.

In the infancy of fetal surgery, there was an emphasis on first developing the techniques for accessing the fetus. As such, in the early days, a standard thoracoabdominal stapler was tested in nonhuman primates to be able to open the gravid uterus while preventing the mother from hemorrhaging. However, it was later discovered that the staples acted similarly to an intrauterine device, and the primates could not get pregnant again. In order to address the fertility problem, a unique absorbable stapler was developed (in partnership with Ethicon – no patents were filed). A recent survey of mothers who had undergone fetal surgery and had subsequent pregnancies demonstrated no difference in fertility following fetal surgery compared to prefetal surgical rates. Due to these other maternal considerations including a higher rate of preterm labor and delivery in mothers who have had fetal surgery, improved surgical outcomes for the mother constitute an optimal portion of the standard of fetal surgery and arise as much from technique innovations as from medical innovations.

Overall, the Achilles heel for fetal surgery was and remains the control and prevention of preterm labor. Until the issue of preterm birth after fetal surgery is solved, the potential addition of prematurity to the fetus’ underlying diagnosis must be weighed against any potential benefit of prenatal intervention.

Fetal Surgery by System

What follows is an introduction to active areas of fetal intervention as categorized by organ system. The reader should note that this is not meant to be an exhaustive list of all disease processes that are amenable to prenatal intervention, as that is beyond the scope of this chapter.